The path of DNA in the kinetochore.
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Biomedical subjects
Shantanu Sharma
Publications and source records attributed to Shantanu Sharma.
Structure alignment via Delaunay tetrahedralization.
A novel protein structure alignment technique has been developed reducing much of the secondary and tertiary structure to a sequential representation greatly accelerating many structural computations, including alignment. Constructed from incidence relations in the Delaunay tetrahedralization, alignments of the sequential representation describe structural similarities that cannot be expressed with rigid-body superposition and complement existing techniques minimizing root-mean-squared distance through superposition. Restricting to the largest substructure superimposable by a single rigid-body transformation determines an alignment suitable for root-mean-squared distance comparisons and visualization. Restricted alignments of a test set of histones and histone-like proteins determined superpositions nearly identical to those produced by the established structure alignment routines of DaliLite and ProSup. Alignment of three, increasingly complex proteins: ferredoxin, cytidine deaminase, and carbamoyl phosphate synthetase, to themselves, demonstrated previously identified regions of self-similarity. All-against-all similarity index comparisons performed on a test set of 45 class I and class II aminoacyl-tRNA synthetases closely reproduced the results of established distance matrix methods while requiring 1/16 the time. Principal component analysis of pairwise tetrahedral decomposition similarity of 2300 molecular dynamics snapshots of tryptophanyl-tRNA synthetase revealed discrete microstates within the trajectory consistent with experimental results. The method produces results with sufficient efficiency for large-scale multiple structure alignment and is well suited to genomic and evolutionary investigations where no geometric model of similarity is known a priori.
Algorithms↗
Sequential chemoradiotherapy versus radiotherapy in the management of locally advanced non-small-cell lung cancer.
This prospective randomized trial compared neoadjuvant chemotherapy followed by local-regional radiotherapy (study group) with radiotherapy alone (control group) in 506 patients with locally advanced non-small-cell lung cancer. The study group received three cycles of cisplatin, ifosfamide with Mesna, and mitomycin C at 21-day intervals. Radiotherapy was delivered up to a dose of 60 Gy. Evaluable patients numbered 460. In the study group, 228 patients were assessed for tumor response after chemotherapy: 13 (5.7%) had a complete response; 103 (43.2%), a partial response; 48 (21%) showed no change; and 74 patients (31.1%) had progressive disease. These patients then received chest irradiation, which was well tolerated. On completion of radiotherapy, 16.2% of the study group and 6% of the control group had a complete response. No change was seen in 10.1% of study patients and 15.5% of control patients. Respective rates for disease progression were 27.6% and 42.3%. Actuarial 2-year survival was 20% in the study group and 7.4% in the control group.
Adult↗